GPRC5D protein and RNA expression levels in normal and clonal plasma cells. (A) Cell surface expression of GPRC5D, as determined by MFI, on plasma cells was assessed by flow cytometry in BM samples obtained from 27 NDMM, 22 daratumumab-naïve RRMM, and 25 daratumumab-refractory MM patients and in normal BM from 11 age-matched healthy donors. Groups were compared using Mann-Whitney U test. (B) GPRC5D cell surface protein expression on MM cells was compared with the expression on BM-localized immune cells in the same patient’s samples by Wilcoxon matched-pairs test. (C) The same analysis was performed in BM samples obtained from healthy donors (n = 11). (D) Cell surface expression of BCMA and CD38 on plasma cells in BM samples from the same patients and healthy donors. (E) Gene expression profiling was performed on purified CD138⁺ plasma cells, publicly available datasets were used. mRNA expression of GPRC5D was compared between normal plasma cells obtained from healthy donors and clonal plasma cells from MGUS, SMM and NDMM patients. GPRC5D mRNA expression is plotted as Log2 transformed, MAS5 normalized values. (F) In datasets from 5 large trials (HOVON65, TT2, TT3, MRC IX, and APEX, n = 1421), GPRC5D mRNA expression in MM cells was compared between patients with or without specific cytogenetic abnormalities (gain(1q), del(13q), del(17p), and IGH translocations [t(4;14), t(11;14), and t(MAF)]). Groups were compared using Wilcoxon rank-sum test. (A-F) Each dot represents an individual sample, with box and whiskers, representing median, 25th-75th percentile, and range. (G) Univariate Cox regression analysis was performed to evaluate the effect of GPRC5D expression on progression-free survival and overall survival. *P < .05; ***P < .001; ****P < .0001. ns, not significant.